Abietic acid, a major ingredient in pine resin, is a naturally toxic compound with potential hazard to animals and plants (Gardner D R et al., 1999, Journal of Natural Toxins. 8(1): 27–34). Exposure to such compound may cause various skin and mucosal symptoms, such as allergic dermatoses and contact urticaria (el Sayed F et al., 1995, Contact Dermatitis. 32(6): 361–2; and Estlander et al., 2001, Contact Dermatitis. 44(4): 213–7). Some traditional Chinese medicaments contain the ingredients of dehydroabietic acid and abietic acid, and a number of patients with dermatitis are sensitive to such ingredients (Lee et al., 1997, Journal of Chromatography. A. 763(1–2): 221–6). In addition, occupational exposure to cedar, pinewoods and pine resin (colophony) may cause asthma and chronic lung disease. Some studies suggested that plicatic and abietic acids were the ingredients responsible for inducing asthmatic reactions that occur in cedar-wood and colophony workers (Ayars et al., 1989, Journal of Allergy & Clinical Immunology. 83(3): 610–8). Recently, it is also found that abietic acid may cause a dose and time-dependent destruction of alveolar, tracheal, and bronchial epithelial cells, and may induce sloughing of bronchial epithelial in vivo. However, the mechanisms for the observed cellular toxic effects are currently unknown.
Furthermore, other biological activities of abietic acid have been reported. For instance, abietic acid or derivatives thereof could exhibit inhibitory effects on the activation of Epstein-Barr virus early antigens (Ohtsu et al., 2001, Planta Medica. 67(1): 55–60), the aggregation of platelet (Cheung et al., 1994, Arzneimittel-Forschung. 44(1): 17–25) and thrombosis (Liu et al., 1985, Journal of Traditional Chinese Medicine. 5(2): 115–8). They could also modulate the functions of synapsomal structure of neuronal cells (Nicholson, 1994, Biochemical Society Transactions. 22(2): 226S).
Recently, many intensive studies focus on the antibacterial activity of abietic acid, especially on the interaction of abietic acid with zinc oxide, rosin and other resin acids and their combination (Soderberg et al., 1990, Scandinavian Journal of Plastic & Reconstructive Surgery & Hand Surgery. Supplementum. 22: 1–87; and Soderberg et al., 1991, Scandinavian Journal of Plastic & Reconstructive Surgery & Hand Surgery. 25(1): 19–24). The so-called “antibacterial effects” of abietic acid might be partially caused by the anti-inflammatory activity of abietic acid. Some studies reported that abietic acid could inhibit lipoxygenase pathway at an IC50 of 29.5±1.29 μM and thus decrease the biosynthesis of leukotrienes in vivo and in vitro (Ulusu et al., 2002, Phytotherapy Research. 16(1): 88–90). In addition, abietic acid could inhibit the production of the inflammatory mediator, prostaglandin E2, in lipopolysaccharide-treated macrophages (Fernandez et al., 2001, Journal of Pharmacy & Pharmacology. 53(6): 867–72).
On the other hand, wood-derived compounds such as β-sitosterol have been shown to have estrogenic effects in fish. In fact, a structure analysis revealed that the chemical structure of abietic acid was similar to that of estrogenic, androgenic and steroid hormones, and a treatment with abietic acid could be estrogenic in breast cancer cells such as MCF-7 or T-47D (Mellanen et al., 1996, Toxicology & Applied Pharmacology. 136(2): 381–8).
Abietic acid, an amphipathic molecule, can be purified to a purity of more than 90% (Luong et al., 1999, Electrophoresis. 20(7): 1546–54). Recently, a number of high resolution nuclear magnetic resonance (NMR) studies have been used to analyze the location of abietic acid in cells and the interaction of abietic acid with the components of a plasma membrane to find out the mechanism of the wide actions of abietic acid. The studies indicated that abietic acid was located in the upper part of the palisade structure of a plasma membrane wherein the carboxyl group of abietic acid was in close proximity to the phospholipid ester group of the membrane but did not extend beyond the C4/C7 carbons of the phospholipid molecule of the membrane (Villalain, 1996, Eur. J Biochem. 241: 586–593; Villalain, 1997, Biochimica et Biophysica Acta. 1328(2): 281–9, 1997; Aranda and Villalain, 1997, Biochimica et Biophysica Acta. 1327(2):171–80). However, most of the studies were conducted on synthetic membranes and little experimental evidence linking the molecular features of abietic acid to the biological effects observed in living cells or tissues was provided. In addition, no references have reported the use of abietic acid for affecting the growth of cancer cells or treating cancers.